Directed Evolution: Bringing New Chemistry to Life

Angewandte Chemie International Edition, Journal Year: 2017, Volume and Issue: 57(16), P. 4143 - 4148

Published: Oct. 24, 2017

Tailor-made: Discussed herein is the ability to adapt biology's mechanisms for innovation and optimization solving problems in chemistry engineering. The evolution of nature's enzymes can lead discovery new reactivity, transformations not known biology, reactivity inaccessible by small-molecule catalysts.

Language: Английский

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Engineering new catalytic activities in enzymes

Nature Catalysis, Journal Year: 2020, Volume and Issue: 3(3), P. 203 - 213

Published: Jan. 20, 2020

Language: Английский

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Expanding the medicinal chemistry synthetic toolbox

Nature Reviews Drug Discovery, Journal Year: 2018, Volume and Issue: 17(10), P. 709 - 727

Published: Aug. 24, 2018

Language: Английский

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A comprehensive metabolic map for production of bio-based chemicals

Nature Catalysis, Journal Year: 2019, Volume and Issue: 2(1), P. 18 - 33

Published: Jan. 8, 2019

Language: Английский

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Systems Metabolic Engineering Strategies: Integrating Systems and Synthetic Biology with Metabolic Engineering

Trends in biotechnology, Journal Year: 2019, Volume and Issue: 37(8), P. 817 - 837

Published: Feb. 5, 2019

Language: Английский

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Directed Evolution: Methodologies and Applications

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(20), P. 12384 - 12444

Published: July 23, 2021

Directed evolution aims to expedite the natural process of biological molecules and systems in a test tube through iterative rounds gene diversifications library screening/selection. It has become one most powerful widespread tools for engineering improved or novel functions proteins, metabolic pathways, even whole genomes. This review describes commonly used diversification strategies, screening/selection methods, recently developed continuous strategies directed evolution. Moreover, we highlight some representative applications nucleic acids, genetic circuits, viruses, cells. Finally, discuss challenges future perspectives

Language: Английский

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Directed Evolution of Protein Catalysts

Annual Review of Biochemistry, Journal Year: 2018, Volume and Issue: 87(1), P. 131 - 157

Published: March 1, 2018

Directed evolution is a powerful technique for generating tailor-made enzymes wide range of biocatalytic applications. Following the principles natural evolution, iterative cycles mutagenesis and screening or selection are applied to modify protein properties, enhance catalytic activities, develop completely new catalysts non-natural chemical transformations. This review briefly surveys experimental methods used generate genetic diversity screen select improved enzyme variants. Emphasis placed on key challenge, namely how novel activities that expand scope reactions. Two particularly effective strategies, exploiting promiscuity rational design, illustrated by representative examples successfully evolved enzymes. Opportunities extending these approaches more complex systems also considered.

Language: Английский

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The Crucial Role of Methodology Development in Directed Evolution of Selective Enzymes

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(32), P. 13204 - 13231

Published: July 3, 2019

Directed evolution of stereo-, regio-, and chemoselective enzymes constitutes a unique way to generate biocatalysts for synthetically interesting transformations in organic chemistry biotechnology. In order this protein engineering technique be efficient, fast, reliable, also relevance synthetic chemistry, methodology development was still is necessary. Following description early key contributions, review focuses on recent developments. It includes optimization molecular biological methods gene mutagenesis the design efficient strategies their application, resulting notable reduction screening effort (bottleneck directed evolution). When aiming laboratory selectivity activity, second-generation versions Combinatorial Active-Site Saturation Test (CAST) Iterative Mutagenesis (ISM), both involving saturation (SM) at sites lining binding pocket, have emerged as preferred approaches, aided by silico such machine learning. The recently proposed Focused Rational Site-specific (FRISM) fusion rational evolution. On-chip solid-phase chemical synthesis rapid library construction enhances quality notably eliminating undesired amino acid bias, future evolution?

Language: Английский

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Pseudomonas putida as a functional chassis for industrial biocatalysis: From native biochemistry to trans-metabolism

Metabolic Engineering, Journal Year: 2018, Volume and Issue: 50, P. 142 - 155

Published: May 16, 2018

The itinerary followed by Pseudomonas putida from being a soil-dweller and plant colonizer bacterium to become flexible engineer-able platform for metabolic engineering stems its natural lifestyle, which is adapted harsh environmental conditions all sorts of physicochemical stresses. Over the years, these properties have been capitalized biotechnologically owing expanding wealth genetic tools designed deep-editing P. genome. A suite dedicated vectors inspired in core tenets synthetic biology enabled suppress many naturally-occurring undesirable traits native this species while enhancing appealing properties, also import catalytic activities attributes other biological systems. Much biotechnological interest on distinct architecture central carbon metabolism. biochemistry naturally geared generate reductive currency [i.e., NAD(P)H] that makes phenomenal host redox-intensive reactions. In some cases, editing indigenous biochemical network (cis-metabolism) has sufficed obtain target compounds industrial interest. Yet, main value promise (in particular, strain KT2440) resides not only capacity heterologous pathways microorganisms, but altogether artificial routes (trans-metabolism) making complex, new-to-Nature molecules. number examples are presented substantiating worth as one favorite workhorses sustainable manufacturing fine bulk chemicals current times 4th Industrial Revolution. potential extend rich beyond existing boundaries discussed research bottlenecks end identified. These aspects include just innovative design new strains incorporation novel chemical elements into extant biochemistry, well genomic stability scaling-up issues.

Language: Английский

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Extending the application of biocatalysis to meet the challenges of drug development

Nature Reviews Chemistry, Journal Year: 2018, Volume and Issue: 2(12), P. 409 - 421

Published: Nov. 20, 2018

Language: Английский

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